<scp>m6A</scp> ‐Related Regulation of Ferroptosis Contributes to Nasal Epithelial Barrier Dysfunction in Allergic Rhinitis

ABSTRACT Background Ferroptosis is a non‐apoptotic form of cell death driven by lipid peroxidation. Although elevated lipid peroxidation has been linked to respiratory epithelial injury, its role in allergic rhinitis (AR) remains unclear. Therefore, in this study, we aimed to assess the role of ferroptosis in AR pathogenesis and elucidate its molecular mechanism. Methods Human nasal epithelial cells (HNEpC and RPMI‐2650) and Balb/c mice were used to evaluate house dust mite (HDM)‐induced ferroptosis related responses and nasal epithelial barrier disruption. Clinical nasal mucosal samples were collected to validate key experimental findings. N6‐methyladenosine (m6A) methylation levels were assessed by m 6 A assays and dot blot analysis, predicted m 6 A sites were identified using SRAMP, and RIP‐qPCR and MeRIP‐qPCR were performed to examine RNA–protein interactions and site‐specific m6A enrichment, respectively. Results HDM exposure induced lipid peroxidation–driven ferroptosis‐related epithelial barrier disruption. Glutathione peroxidase 4 (GPX4) acted as a protective regulator, as ferroptosis inhibition or GPX4 overexpression alleviated epithelial damage. Growth arrest‐specific 1 (GAS1) promoted ferroptosis by suppressing GPX4 expression, a finding further supported by in vivo validation in GAS1‐knockdown mice. Mechanistically, this GAS1–GPX4 regulatory relationship was linked to METTL3‐mediated m 6 A modification of GPX4 mRNA at the site 625. Conclusions These findings suggest a novel mechanism whereby HDM exposure promotes ferroptosis‐related nasal epithelial barrier impairment through GAS1–METTL3–mediated regulation of GPX4 m 6 A methylation, thereby contributing to AR pathogenesis.